Hyaluronan regulates ceruloplasmin production by gliomas and their treatment-resistant multipotent progenitors.
Ceruloplasmin (glycosylphosphatidylinositol-linked ferroxidase associated with normal astrocytes) can also be secreted by glioma cells, where its function is unknown. Ceruloplasmin is not only present in glioma cells and in human glioma specimens but also is enriched in highly malignant glioma stem-like cells. Hyaluronan is a large extracellular glycosaminoglycan that enhances malignant glioma behaviors by interacting with CD44 receptors and by downstream activation of signaling proteins and transporters associated with malignancy. We examined the relationship between hyaluronan and ceruloplasmin expression in glioma stem-like cells. Antagonism of hyaluronan interactions with short-fragment hyaluronan oligomers decreased ceruloplasmin expression in parental and stem-like glioma cells in vivo and in cell culture, implying that hyaluronan regulates ceruloplasmin expression. Further gain and loss-of-function studies are needed to fully define the relationship between hyaluronan and ceruloplasmin, and ceruloplasmin's effect on malignant behaviors.
Tye
Sandra L
SL
Department of Pediatrics, Charles P Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, South Carolina 29425, USA.
Gilg
Anne G
AG
Tolliver
Lauren B
LB
Wheeler
William G
WG
Toole
Bryan P
BP
Maria
Bernard L
BL
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002570:Ceruloplasmin / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism* / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013120:Spinal Cord Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D002570:Ceruloplasmin